Department of Dermatology and Venerology, University Hospital of Cologne
Cluster of Excellence - Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne
Our work is mainly focused on embryonic development in the mouse which takes about 19 days. We are interested in mouse embryonic development around the beginning of gastrulation (embryonic days E6.5-E7.5 in the mouse) as well as skin development (E12.5-E17.5). We study the roles of signaling pathways and cytoskeletal organizers in cell fate choices during these developmental processes.
1) Centrosomes in mouse development
Centrosomes are major microtubule organizing centers of animal cells. During interphase or in differentiated cells, the centrosome is essential to provide the template for cilia and flagella, whereas during cell division the centrosome is required for the efficient assembly of the mitotic spindle. Using genetic mutations in the mouse, we have previously removed centrosome function in the developing mouse embryo and brain. The main result was the activation of a p53-dependent apoptosis pathway that was not due to the secondary loss of cilia and was linked to prolonged mitosis. We and others have shown that this novel checkpoint is also independent of DNA damage or abnormalities in chromosome segregation. Our group is using genetics and biochemistry to unravel the mechanism of this novel checkpoint in mouse embryos and mESCs. Our aim is to shed light on centrosome-related human diseases and to help find ways of treating them.
2) Centrosomes in skin epithelial development
Centrosomes regulate mitotic spindle orientation which has been linked with the mode of progenitor cell division (symmetric versus asymmetric divisions). The skin epidermis is an ideal system to investigate the roles of centrosomes and cell division in determining cell fate during embryonic development and adult homeostasis. We are using genetic approaches to investigate the roles of centrosomes and cilia in cell fate specification in the skin epithelium.
3) The STRIPAK complex in the skin
The striatin-interacting phosphatases and kinases complexes (STRIPAK) are biochemical complexes that regulate the balance of the activities of the phosphatase PP2A and associated kinases. We have shown that striatin-interacting protein 1 (STRIP1), a core component of the STRIPAK, is essential for normal mesoderm formation and migration in the mouse embryo through regulation of the actin cytoskeleton organization (Figure from Bazzi et al, 2017). We are studying the roles of the STRIPAK in the epithelial and mesenchymal cells in the skin .
4) Hair follicle development and patterning
The first hair follicles in mouse skin develop around E14 through an interaction between the mesenchyme and the overlying epithelium and are precisely spaced and patterned. We are using transcriptomics and genetic approaches in the mouse to study the signaling hierarchies in hair follicle morphogenesis.